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| | Andrew Simcox is the name his parents gave him and he totally loves this name. It's not a common factor but what I like performing is to climb but I don't have the time lately. Office supervising is exactly where her primary income comes from. For a whilst I've been in Alaska but I will have to transfer in a year or two.<br><br>Feel free to visit my blog; clairvoyance [[http://203.250.78.160/zbxe/?document_srl=1792908 203.250.78.160]] |
| {{enzyme
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| | Name = tryptophan 5-monooxygenase
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| | EC_number = 1.14.16.4
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| | CAS_number = 9037-21-2
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| | IUBMB_EC_number = 1/14/16/4
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| | GO_code = 0004510
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| | image =
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| | width =
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| | caption =
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| }}
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| {{protein
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| | Name = [[TPH1|tryptophan hydroxylase 1 (tryptophan 5-monooxygenase)]]
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| | caption =
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| | image =
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| | width =
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| | HGNCid = 12008
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| | Symbol = [[TPH1]]
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| | AltSymbols = TPRH, TPH
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| | EntrezGene = 7166
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| | OMIM = 191060
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| | RefSeq = NM_004179
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| | UniProt = P17752
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| | PDB = 1MLW
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| | ECnumber = 1.14.16.4
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| | Chromosome = 11
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| | Arm = p
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| | Band = 15.3
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| | LocusSupplementaryData = -p14
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| }}
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| {{protein
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| | Name = [[TPH2|tryptophan hydroxylase 2]]
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| | caption =
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| | image =
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| | width =
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| | HGNCid = 20692
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| | Symbol = [[TPH2]]
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| | AltSymbols =
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| | EntrezGene = 121278
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| | OMIM = 607478
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| | RefSeq = NM_173353
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| | UniProt = Q8IWU9
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| | PDB =
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| | ECnumber =
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| | Chromosome = 12
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| | Arm = q
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| | Band = 15
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| | LocusSupplementaryData =
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| }}
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| {{stack end}}
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| '''Tryptophan hydroxylase''' ('''TPH''') is an [[enzyme]] ({{EC number|1.14.16.4}}) involved in the synthesis of the neurotransmitter [[serotonin]]. TPH catalyzes the following chemical reaction
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| : L-[[tryptophan]] + [[tetrahydrobiopterin]] + O<sub>2</sub> <math>\rightleftharpoons</math> [[5-Hydroxytryptophan]] + dihydrobiopterin + H<sub>2</sub>O
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| It employs one additional [[cofactor (biochemistry)|cofactor]], [[iron]]. | |
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| == Function ==
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| {{stack|
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| {{Enzymatic Reaction
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| |foward_enzyme=Tryptophan hydroxylase
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| |reverse_enzyme=
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| |substrate=[[Tryptophan]]
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| |product=[[5-HTP]]
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| |reaction_direction_(forward/reversible/reverse)=forward
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| |minor_foward_substrate(s)=O<sub>2</sub><br />[[Tetrahydrobiopterin|BH<sub>4</sub>]]
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| |minor_foward_product(s)=H<sub>2</sub>O<br />BH<sub>2</sub>
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| |minor_reverse_substrate(s)=
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| |minor_reverse_product(s)=
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| |substrate_image=Tryptophan_simple.png
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| |substrate_image_size=120px
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| |product_image=5-hydroxytryptophan.png
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| |product_image_size=120px
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| }}
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| }}
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| It is responsible for addition of the -HO group ([[hydroxylation]]) to the 5 position to form the [[amino acid]] [[5-hydroxytryptophan]] (5-HTP), which is the initial and rate-limiting step in the synthesis of the neurotransmitter serotonin. It is also the first enzyme in the synthesis of melatonin.
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| Tryptophan hydroxylase (TPH), tyrosine hydroxylase (TH) and phenylalanine hydroxylase (PAH)
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| are members of a superfamily of aromatic amino acid hydroxylases, catalyzing key steps in important metabolic pathways.<ref name="pmid11747434">{{cite journal | author = McKinney J, Teigen K, Frøystein NA, Salaün C, Knappskog PM, Haavik J, Martínez A | title = Conformation of the substrate and pterin cofactor bound to human tryptophan hydroxylase. Important role of Phe313 in substrate specificity | journal = Biochemistry | volume = 40 | issue = 51 | pages = 15591–601 |date=December 2001 | pmid = 11747434 | doi = 10.1021/bi015722x | url = http://www.bh4.org/pdf/mckinney.pdf }}</ref> Analogously to [[phenylalanine hydroxylase]] and [[tyrosine hydroxylase]], this enzyme uses (6R)-L-erythro-5,6,7,8-[[tetrahydrobiopterin]] (BH<sub>4</sub>) and dioxygen as cofactors.<ref name="urlBH4 Databases">{{cite web | url = http://www.bh4.org/BH4_Deficiency_Biochemistry.asp | title = tetrahydrobiopterin | author = | authorlink = | coauthors = | year = 2005 | format = | work = BH4 Databases | publisher = BH4.org | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = }}</ref>
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| In humans, the stimulation of serotonin production by administration of tryptophan has an antidepressant effect{{Citation needed|date=November 2008}} and inhibition of tryptophan hydroxylase (e.g. by [[p-Chlorophenylalanine]]) may precipitate depression.<ref name="pmid12379098">{{cite journal | author = Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC | title = Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin | journal = Biochemistry | volume = 41 | issue = 42 | pages = 12569–74 |date=October 2002 | pmid = 12379098 | doi = 10.1021/bi026561f | url = }}</ref>
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| The [[Enzyme activity|activity]] of tryptophan hydroxylase (i.e. the rate at which it converts L-tryptophan into the serotonin precursor L-5-hydroxytryptophan) can be increased when it undergoes [[phosphorylation]]. [[Protein Kinase A]], for example, can phosphorylate tryptophan hydroxylase, thus increasing its activity.
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| == Isoforms ==
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| In humans, as well as in other mammals, there are two distinct TPH genes. In humans, these genes are located on chromosomes 11 and 12 and encode two different homologous enzymes ''[[TPH1]]'' and ''[[TPH2]]'' (sequence identity 71%).<ref name="pmid14563478">{{cite journal | author = Walther DJ, Bader M | title = A unique central tryptophan hydroxylase isoform | journal = Biochem. Pharmacol. | volume = 66 | issue = 9 | pages = 1673–80 |date=November 2003 | pmid = 14563478 | doi = 10.1016/S0006-2952(03)00556-2| url = }}</ref>
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| *TPH1 is mostly expressed in tissues that express serotonin (a neurotransmitter) in the periphery ([[skin]], [[Gut (zoology)|gut]], [[pineal gland]]) but it is also expressed in the central nervous system.
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| *On the other hand, TPH2 is exclusively expressed in [[neuronal]] cell types and is the predominant isoform in the [[central nervous system]].
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| == Additional images ==
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| <gallery>
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| Image:5htsynt 2.png |The pathway for the synthesis of serotonin from tryptophan
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| Image:Trp-5ht-pathway.svg |Metabolic pathway from tryptophan to serotonin
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| </gallery>
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| == References ==
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| {{reflist}}
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| == Further reading ==
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| {{refbegin | 2}}
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| * {{cite journal | author = Friedman PA, Kappelman AH, Kaufman S | year = 1972 | title = Partial purification and characterization of tryptophan hydroxylase from rabbit hindbrain | journal = J. Biol. Chem. | volume = 247 | pages = 4165–73 | pmid = 4402511 | issue = 13 }}
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| * {{cite journal | author = Hamon M, Bourgoin S, Artaud F, Glowinski J | year = 1979 | title = The role of intraneuronal 5-HT and of tryptophan hydroxylase activation in the control of 5-HT synthesis in rat brain slices incubated in K+-enriched medium | journal = J. Neurochem. | volume = 33 | pages = 1031–42 | pmid = 315449 | doi = 10.1111/j.1471-4159.1979.tb05239.x | issue = 5 }}
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| * {{cite journal | author = Ichiyama A, Nakamura S, Nishizuka Y, Hayaishi O | year = 1970 | title = Enzymic studies on the biosynthesis of serotonin in mammalian brain | journal = J. Biol. Chem. | volume = 245 | pages = 1699–709 | pmid = 5309585 | issue = 7 }}
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| * {{cite journal | author = Jequier E, Robinson DS, Lovenberg W, Sjoerdsma A | year = 1969 | title = Further studies on tryptophan hydroxylase in rat brainstem and beef pineal | journal = Biochem. Pharmacol. | volume = 18 | pages = 1071–81 | pmid = 5789774 | doi = 10.1016/0006-2952(69)90111-7 | issue = 5 }}
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| * {{cite journal | author = Wang L, Erlandsen H, Haavik J, Knappskog PM, Stevens RC | year = 2002 | title = Three-dimensional structure of human tryptophan hydroxylase and its implications for the biosynthesis of the neurotransmitters serotonin and melatonin | journal = Biochemistry. | volume = 41 | pages = 12569–74 | pmid = 12379098 | doi = 10.1021/bi026561f | issue = 42 }}
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| * {{cite journal | author = Windahl MS, Petersen CR, Christensen, HEM, Harris P | year = 2008 | title = Crystal Structure of Tryptophan Hydroxylase with Bound Amino Acid Substrate | journal = Biochemistry. | volume = 47 | pages = 12087–94 | pmid = 18937498 | doi = 10.1021/bi8015263 | issue = 46}}
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| {{refend}}
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| == External links ==
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| *{{MeshName|Tryptophan+Hydroxylase}}
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| See also [http://www.proteopedia.org/wiki/index.php/Tryptophan_hydroxylase tryptophan hydroxylase] in [http://www.proteopedia.org Proteopedia]
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| {{Oxygenases}}
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| {{Neurotransmitter metabolism enzymes}}
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| [[Category:EC 1.14.16]]
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| {{1.14-enzyme-stub}}
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Andrew Simcox is the name his parents gave him and he totally loves this name. It's not a common factor but what I like performing is to climb but I don't have the time lately. Office supervising is exactly where her primary income comes from. For a whilst I've been in Alaska but I will have to transfer in a year or two.
Feel free to visit my blog; clairvoyance [203.250.78.160]